Body fluid and cardiovascular homeostasis depends on ingestive behaviors and on reflexes acting to modulate renal water and sodium loss and to redistribute blood flow. In order for the appropriate effector mechanisms that maintain body fluid balance and cardiovascular function to be engaged, the brain must receive information about the current status of body hydration and blood pressure. Several visceral sensory systems provide this type of information to the central nervous system (CNS). This input is carried over afferent neural pathways and by the direct action of circulating factors on select brain regions which lack a blood-brain barrier. Three permeable areas of the brain receiving blood-borne signals have been described as sensory circumventricular organs (CVOs) and are typified by the subfornical organ (SFO). This proposal focuses on the SFO and its role in detecting circulating angiotensin II, how this information is handled within this structure and ultimately transferred into forebrain regions involved in the behavioral and reflex control of hydromineral balance and blood pressure. The present proposal builds upon our prior studies of the central sensing and processing of afferent signals involved in body fluid and cardiovascular homeostasis. The aims of this research are to investigate the mechanisms of sensory transfer and neural processing with the SFO in response to blood-borne ANG II and then to characterize the pathways which convey this information to specific forebrain nuclei involved in maintaining cardiovascular and body fluid homeostasis. The studies will employ both in vivo and in vitro methods to electrophysiologically, pharmacologically and anatomically characterize identified cells with the SFO. The cells will be analyzed to understand the mechanisms they use for both intra- and inter- cellular signaling. New information derived from studies on this important sensory structure that couples the systemic circulation with the CNS proper has relevance for understanding both normal physiology and pathophysiology associated with states of disordered body fluid and cardiovascular regulation, such as in hypertension.